Disseminated neoplasia and large foci indicating heavy haemocytic infiltration in cockles Cerastoderma edule from Galicia (NW Spain).

A histopathological survey was performed to search for the cause of high mortality in the cockle Cerastoderma edule in northern rias of Galicia (northwestern Spain). From limited sampling, 2 severe pathological conditions with high prevalence were found: disseminated neoplasia and the occurrence of numerous, large foci of heavy haemocytic infiltration. Both conditions were detected in areas affected by high mortality and were absent (foci of haemocytic infiltration) or with lower prevalence (disseminated neoplasia) in an area with unnoticeable mortality that was chosen as a reference. Advanced cases of both pathological conditions were associated with extensive tissue destruction. Because of the severity of the lesions and their high prevalence, both pathological conditions could have contributed to the high mortality.     

Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection.

The contribution of endogenous NK cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. In immunocompetent C57BL/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. The inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression. The largest number of necrotic foci was found 2 days after infection. Overall hepatic damage, assessed as increased expression of liver enzymes in serum, accompanied the development of inflammatory and necrotic foci. Experiments with neutralizing antibodies demonstrated that although virus-induced tumor necrosis factor (TNF) can have antiviral effects, it also mediated significant liver pathology. TNF was required for development of hepatic necrotic foci and increased levels of liver enzymes in serum but not for increased numbers of inflammatory foci. The necrotic foci and liver enzyme indications of pathology occurred independently of NK and T cells, because mice rendered NK-cell deficient by treatment with antibodies, T- and B-cell-deficient Rag-/- mice, and NK- and T-cell-deficient E26 mice all manifested both parameters of disease. Development of necrotic foci and maximally increased levels of liver enzymes in serum also were TNF dependent in NK-cell-deficient mice. Moreover, in the immunodeficient E26 mice, virus-induced liver disease was progressive, with eventual death of the host, and neutralization of TNF significantly increased longevity. These results establish conditions separating hepatitis from significant liver damage and demonstrate a cytokine-mediated component to viral pathogenesis.     

Hemorrhagic enteritis in captive American kestrels (Falco sparverius)

Hemorrhagic enteritis and hepatitis of suspected adenovirus etiology were the apparent cause of death of nine captive American kestrels. Cloacal hemorrhage was the only prominent gross lesion: disseminated hepatocellular necrosis, and intranuclear inclusion bodies were evident microscopically. Electron microscopy revealed numerous adenovirus-like particles associated with the hepatic lesions. Attempts to serologically identify the agent were unsuccessful.     

Acute disseminated toxoplasmosis in a red fox (Vulpes vulpes)

A red fox (Vulpes vulpes) with signs of neurological disease was captured in Fairmount Park, Philadelphia, Pennsylvania (USA). The animal died in captivity and was examined because of suspected rabies. The liver had pale foci up to 4 mm in diameter. Foci of necrosis were associated with Toxoplasma gondii tachyzoites in several organs including liver, lungs and adrenal glands. Rabies antigen and distemper virus inclusions were not detected. The diagnosis of acute disseminated toxoplasmosis was confirmed by immunohistochemical staining.     

Detection of gamma glutamyl transpeptidase in the livers of germfree and conventional rats

Germfree and conventional rats, 1-41 months of age, were examined for gamma glutamyl transpeptidase in frozen sections prepared from their livers. This histochemical marker has been associated with early changes which develop following exposure to known carcinogenic agents. Positive gamma glutamyl transpeptidase markers were detected in 86% of germfree rats over 4 months of age, and the gamma glutamyl transpeptidase foci were larger and more numerous as the animals aged, and the foci were prominent in rats with hepatic tumors. Gamma glutamyl transpeptidase foci were observed in 96% of livers from conventional rats at 11-20 months of age. The agents responsible for induction of the gamma glutamyl transpeptidase foci in the liver were not identified.     

Disseminated cytomegalovirus disease in the guinea pig

Two guinea pigs (Cavia porcellus), which were housed conventionally in separate animal facilities and had not been experimentally manipulated, were found to have evidence of disseminated cytomegalovirus disease at necropsy. Microscopic examination revealed multiple focal areas of necrosis in numerous organs. The spleen, liver, kidney and lungs were affected particularly. These lesions contained numerous cells with large intranuclear and cytoplasmic inclusion bodies resembling cytomegalovirus inclusions. Characteristic cytomegalovirus virions were observed by electron microscopy in both cases. Antigens of guinea pig cytomegalovirus were detected in paraffin sections of lesions from both cases with an immunoperoxidase technique. Although subclinical infection is common, this is the only contemporary report of disseminated disease due to cytomegalovirus in guinea pigs.     

An infection of cow with Mortierella wolfii

A Japanese black cow from a farm in Gunma prefecture showed pyrexia, anorexia and depression. An autopsy revealed hepatic lesions consisting of numerous approximately spherical pale lesions scattered about on the surface and cut parts. The inflammatory lesions were observed in the right lobe of the lung. A part of the trachea was whitish and thickened. Histologically, necrotic foci were observed throughout most of the liver with fungal proliferation about the blood vessels. The lesions of the lung were seriously exudative and the fungus was also present in some of the bronchiole and on bloodvessel walls. Mortierella wolfii was isolated from the liver. The hyphae in the liver were identical in appearance with those seen in the tissues of rabbits experimentally inoculated with M. wolfii.This report is the first case of M. wolfii infection in Japan     

Hemorrhagic fever with renal syndrome: clinical aspects

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral fever which typically progresses through five stages: an acute grippe, followed by hemorrhage and shock, acute renal insufficiency from tubulo-interstitial nephritis, and recovery. Death from circulatory or renal failure occurs in 5%-15% of cases. In mild or abortive forms of the disease, associated with viral strains enzootic in Scandinavia the illness is milder. Hemorrhage and shock occur with lower frequency and the fatality rate is less than 1%. Pathologic examination of HFRS cases from Asia discloses generalized congestion, hyperemia, and hemorrhage, with scattered foci of necrosis in numerous organs. Congestion and hemorrhage are most evident in the kidney medulla. Widespread microscopic evidence of capillary and vascular dysfunction is found, with endothelial cell swelling, perivascular edema, diapadesis of erythrocytes and mononuclear cell infiltration. Hemorrhage and inflammation in the renal interstitium and tubular epithelial degeneration characterize the kidney pathology. Limited data indicate pathogenic roles for cell destruction from viral infection as well as immune mediated mechanisms. No specific therapy is available.     

Experimental simian varicella virus infection of St. Kitts vervet monkeys

Experimental simian varicella virus (SVV) infection of St. Kitts vervet monkeys was evaluated as an animal model to investigate human varicella-zoster virus (VZV) infections. During the incubation period, viremia disseminated infectious virus throughout the body via infected peripheral blood lymphocytes (PBLs). A vesicular skin rash in the inguinal area, and on the abdomen, extremities, and face appeared on day 7–10 postinfection. Necrosis and hemorrhage in lung and liver tissues from acutely infected monkeys were evident upon histologic analysis. Recovery from simian varicella was accompanied by a rise in the serum neutralizing antibody response to the virus. SVV latency was established in trigeminal ganglia of monkeys which resolved the acute infection. This study indicates that experimental SVV infection of St. Kitts vervets is a useful animal model to investigate SVV and VZV pathogenesis and to evaluate potential antiviral agents and vaccines.     

Disseminated toxoplasmosis in magpie geese (Anseranas semipalmata) with large numbers of tissue cysts in livers

Fatal disseminated Toxoplasma gondii infection was diagnosed in 2 captive magpie geese (Anseranas semipalmata) from a zoo in Texas. Both geese died suddenly, without apparent clinical signs. Lesions associated with T. gondii tachyzoites were seen in lungs, pancreas, liver, adrenals, bursa of Fabricius, spleen, brain, and kidneys. Toxoplasmic pneumonia and hepatitis were considered to be the primary cause of death. An unusual feature was the presence of numerous tissue cysts in hepatocytes of both geese. The diagnosis was confirmed immunohistochemically. Antibodies to T. gondii were found in 2 of 11 other geese from the zoo examined using the modified agglutination test. This is the first report of T. gondii infection in magpie geese (Anseranas semipalmata).     

A clinical,pathological, and mycological study of a fatal case of histoplasmosis in an infant

Summary The clinical history of a fatal case of acute disseminated Histoplasmosis in a 3-month-old infant is described. A liver biopsy performed ante mortem revealed numerous encapsulated organisms which were identified at H.capsulatum. This suggests the applicability of this technique as a diagnostic tool. An autopsy showed extensive involvement, the organisms being found in the lungs, thymus, mediastinal and retroperitoneal nodes, liver, adrenals, spleen, and kidneys.A portion of emulsified liver was inoculated into Swiss mice andH. capsulatum was recovered from the mouse tissues 4 weeks after inoculation.A study was made of the cultural characteristic of this culture and it conformed to those previously described for other strains. A study of its fermentation properties disclosed no acid or gas production in media containing glucose, sucrose, lactose, maltose, mannose, rhamnose, trehalose, dulcitol, sorbitol, mannitol, and xylose.     

Inclusion body disease in a great horned owl.

The carcass of a great horned owl (Bubo virginianus), which had been found moribund in southern Ontario, was presented for necropsy. Throughout the liver and spleen were numerous white foci 1-2 mm in diameter; also noted were white plaques in the mucosae of the pharyngeal papillae and intestine. Results of light and electron microscopic studies and experimental transmission to two captive great horned owls suggested that this was a herpvirus disease similar and possibly indentical to the owl disease reported by other workers in Wiconsin and Australia.     

Biomarkers of Residual Disease,Disseminated Tumor Cells,and Metastases in the MMTV-PyMT Breast Cancer Model

Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment of these disease states prior to their development into metastases and recurrent tumors. Here we describe the molecular profiling of disseminated tumor cells in lungs, lung metastases, and residual tumor cells in the MMTV-PyMT breast cancer model. MMTV-PyMT mice were bred with actin-GFP mice, and focal hyperplastic lesions from pubertal MMTV-PyMT;actin-GFP mice were orthotopically transplanted into FVB/n mice to track single tumor foci. Tumor-bearing mice were treated with TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide), and residual and relapsed tumor cells were sorted and profiled by mRNA microarray analysis. Data analysis revealed enrichment of the Jak/Stat pathway, Notch pathway, and epigenetic regulators in residual tumors. Stat1 was significantly up-regulated in a DNA-damage-resistant population of residual tumor cells, and a pre-existing Stat1 sub-population was identified in untreated tumors. Tumor cells from adenomas, carcinomas, lung disseminated tumor cells, and lung metastases were also sorted from MMTV-PyMT transplant mice and profiled by mRNA microarray. Whereas disseminated tumors cells appeared similar to carcinoma cells at the mRNA level, lung metastases were genotypically very different from disseminated cells and primary tumors. Lung metastases were enriched for a number of chromatin-modifying genes and stem cell-associated genes. Histone analysis of H3K4 and H3K9 suggested that lung metastases had been reprogrammed during malignant progression. These data identify novel biomarkers of residual tumor cells and disseminated tumor cells and implicate pathways that may mediate metastasis formation and tumor relapse after therapy.     

Studies on relationship between cysts and granulomas in murine cryptococcosis

The histopathology of murine cryptococcosis was observed until the 55th day and particular attention was paid to whether or not cysts, which had been formed in the brain, could change to granulomas. Cryptococcus neoformans RIB-12M was used in this experiment. As experimental animals, five-week-old male BALB/c mice, weighing 20–22 g, were used. An infective inoculum was prepared by adjusting the number of cryptococci to 10⁶ or 5 × 10⁶/0.2 ml. Each mouse was inoculated intravenously with 0.2 ml of the cell suspension, and the colony forming unit of the brain and liver, and the histopathological findings in various visceral organs were investigated.40 × 10⁴ colonies grew from 100 mg of the brain tissue of the eighth day. Thereafter, the number increased gradually. It reached 500 × 10⁴ on the 20th day. The colony forming unit from the liver reached a peak on the 12th day (250 × 10⁴) and thereafter the number decreased gradually.Histopathologically, the brain and liver were severely affected with the fungus. In the brain cysts with cryptococci continued to increase until the end of the experiment. On the other hand, in the liver several purulent foci appeared on the second day. On the eighth day numerous mononuclear cells accumulated at the foci and their lesions changed to granulomatous ones with cryptococci. The number of granulomatous lesions reached a peak on the 16th day in the mice inoculated with 5 × 10⁶ cryptococci, and thereafter showed a tendency to decrease gradually.     

Early effects in chemical-induced rat liver carcinogenesis: an immunohistochemical study following exposure to 0.04% AAF

To investigate effects that distinguish AAF from incomplete carcinogens, the rate of cell death (apoptosis) and cell proliferation was studied at early stages of AAF induced rat liver carcinogenesis. Male Wistar rats were fed 0.04% AAF in the diet for 2, 6 and 16 weeks and immunohistochemical markers were measured in the liver. The formation of initiated cells and preneoplastic foci was followed by staining for GST-P (glutathione-S-transferase). GST-P-positive foci were present from 6 weeks on. Apoptosis was increased in the periportal area and in preneoplastic foci at all time points. Cell proliferation was enhanced in the periportal area in oval cells and in bile duct-like cells particularly at 2 and 6 weeks and mainly in GST-P positive foci at 16 weeks. Notably, more cells always proliferated than were eliminated. Other apoptosis-related markers like p53 and FAS/Apo-1 could not be demonstrated in either normal hepatocytes, preneoplastic foci or in hepatocytes from treated animals. Scattered bcl-2 positive cells were present in livers at 16 weeks of treatment. The two cell growth and differentiation related proto-oncogenes c-FOS and c-JUN were increased in all treated animals at early stages. If feeding was stopped after 6 weeks, livers did not recover significantly within the following 10 weeks. The results support the complex effects of AAF in rat liver carcinogenesis. Chronic toxicity locally impairs the balance between cell proliferation and cell death and induces morphological alterations that promote the growth of initiated cells.     

Naturally occurring Yersinia enterocolitica septicemia in patas monkeys (Erythrocebus patas)

Two cases of Yersinia enterocolitica septicemia occurred in a breeding group of 22 adult patas monkeys (Erythrocebus patas). Affected animals had acute clinical signs of depression, weakness, dehydration, hypothermia, hepatomegaly and pronounced leukopenia. Both animals died a few hours after treatment was initiated. Gross necropsy findings included jaundice, fluid in body cavities, hepatomegaly, splenomegaly, multiple white foci within the liver and spleen, generalized lymph node enlargement and numerous mucosal ulcerations in the colon. Primary histopathological lesions were multifocal hepatic necrosis, splenic necrosis, chronic ulcerative enteritis and diaphragmatic myositis with necrosis and edema. Yersinia enterocolitica was cultured from the liver, spleen, lung, jejunum and rectum. Wild rodents, particularly mice, may have been a source of infection for these animals, as the monkeys were housed in a rural, indoor-outdoor facility. A preliminary culture survey showed that some clinically normal patas monkeys harbored the organism in their intestinal tracts.     

An outbreak of "wet tail" in hamsters due to Tyzzer's organism (author's transl)

In a colony of Golden hamsters, many animals were found to show signs of "wet tail", and spontaneous deaths occurred during two months. With this outbreak of wet tail and death, etiologic and pathologic studies were made on 11 cases supplied from the colony. Gross pathologic examination disclosed hemorrhagic enteritis in 10 and necrotic foci in the liver in 5 out of 10 cases examined. A number of bacilli morphologically suggestive of Tyzzer's organisms were detected on smears of cut surfaces of the affected intestines and livers. After inoculation with homogenate of the intestines from the moribund cases into hamsters by oral route, the same clinical manifestations as observed in spontaneous cases were reproduced, and the inoculated animals died in 10 to 14 days with numerous Tyzzer's organisms in their intestines and livers. When apparently healthy hamsters were introduced into contaminated cages with soiled bedding which were allowed to stand at room temperature for about 2 months, most of them developed signs of wet tail and died in 5 to 19 days having liver necrosis characteristic of Tyzzer's disease.     

Disseminated toxoplasmosis in a Mediterranean pregnant Risso's dolphin (Grampus griseus) with transplacental fetal infection

Fatal disseminated toxoplasmosis was diagnosed in a Risso's dolphin (Grampus griseus) dam and its fetus on the basis of pathologic findings, immunohistochemistry, and structure of the parasite. The dolphin was stranded alive on the Spanish Mediterranean coast and died a few hours later. At necropsy the dam was in good condition. From the standpoint of pathology, however, it had generalized lymphadenomegaly and splenomegaly, enlargement of and multifocal hemorrhage in the adrenal glands, diffuse mucosal hemorrhage of the glandular and pyloric stomach, ulcerative glossitis and stomatitis, focal erosions and reddening of the laryngeal appendix, and severe paraotic sinusitis with intralesional nematodes Crassicauda grampicola. The dolphin was pregnant, most probably in the first gestational trimester. The most prominent microscopic lesions were multifocal granulomatous encephalomyelitis, diffuse subacute interstitial pneumonia, mild multifocal necrotizing hepatitis and nonsuppurative cholangiohepatitis, gastritis and adrenalitis, mild lymphoid depletion, medullary sinus and follicular histyocitosis, and systemic hemosiderosis. The fetus had foci of coagulative and lytic necrosis in the kidneys, the lung, and the heart. Most lesions were associated with tachyzoites and tissue cysts of Toxoplasma gondii. The diagnosis was confirmed immunohistochemically. This is the first report on toxoplasmosis in a Risso's dolphin (G. griseus) and on transplacental transmission to an early-stage fetus in any cetaceans.     

Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in a northern spotted owl

Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.     

Alcohol-induced liver cirrhosis as a cause of portal hypertension

Basic data on pathomorphology and symptomatology of the alcohol-induced liver cirrhosis accompanied by portal hypertension are discussed. Respective data were compared with the group of cirrhotic patients not abusing alcohol. A high percentage of encephalopathic disorders and nearly 50% of the patients suffering from the hemorrhage from esophageal varices were the first sign of the cirrhosis in both groups. Despite hemorrhage from esophageal varices a few patients obtained surgical help preventing recurrence of the hemorrhage. Liver functional reserve, incidence of encephalopathies and the degree of liver involvement are in favour for non-alcohol cirrhosis. Inflammatory process in the liver, splenomegaly and hypersplenism were more frequent in the liver cirrhosis of non-alcohol origin.